Annals of Oncology 13:486-487, 2002
© 2002 European Society for Medical Oncology
Letters to the Editor |
Reply to "Letter to the Editor on ‘Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study’", by V. C. G. Tjan-Heijnen, P. E. Postmus & A. Ardizzoni (Ann Oncol 2002; 13: 485–486)
University of Colorado Comprehensive Cancer Center, Denver, CO, USA (E-mail: Paul.Bunn@uchsc.edu)
In response to the letter of Tjan-Heijnen et al. I have the following comments:
1. Selection of chemotherapy. Neither CDE nor CAV have been shown to be superior to a two-drug combination of etoposide/cisplatin, but toxicity is greater on the three-drug regimens. Very few randomized trials have shown an advantage for the use of any three-drug combination over a two-drug combination, but all have shown significant increases in toxicity. Standard two-drug combinations of etoposide and cisplatin (or carboplatin) produce rates of grade 4 neutropenia and thrombocytopenia of <10% and often <5% [1, 2]. The three-drug combination studied by the authors produced much higher, and clinically relevant, rates of grade 4 neutropenia (45–85%) and thrombocytopenia (5–51%) in all four arms [3]. The three-drug combination studied in this report also produced unacceptably high rates of febrile leukopenia (24–56%) and hospitalizations. Given that there were no differences in efficacy between the treatment arms or between these study results and the two-drug combination study results, I fail to see the rationale for selecting regimens that are more toxic. The results of the most recent randomized intergroup study comparing two-drug (etoposide/cisplatin) with three-drug (paclitaxel/etoposide/cisplatin) regimens will be presented at ASCO in 2002. Then we will see whether newer three-drug combinations will be any different.
2. Role of prophylactic antibiotics. G-CSF and prophylactic antibiotics both reduce the incidence of febrile neutropenia when used in conjunction with chemotherapy regimens that produce high rates of febrile neutropenia. Standard two-drug combinations produce febrile neutropenia in <5% of patients. Neither G-CSF nor prophylactic antibiotics should be used in such a setting. These conclusions could change if a more toxic combination (such as paclitaxel/etoposide/cisplatin as discussed above) was proven to improve survival. Until then, neither toxic regimens, G-CSF or prophylactic antibiotics are routinely indicated. It is difficult to understand the authors contention that oral antibiotics save money by reducing hospitalizations when febrile neutropenias and hospitalization rarely occur on standard two-drug treatment regimens.
3. We agree on the need for additional study in high risk patients such as those with poor performance status and advanced age.
P. Bunn
University of Colorado Comprehensive Cancer Center, Denver, CO, USA (E-mail: Paul.Bunn@uchsc.edu)
References
1.
Ihde DC, Mulshine JL, Kramer BS et al. Prospective randomized comparison of high-dose and standard-dose eotposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol 1994; 12: 2022–2034.
2. Roth BJ, Johnson DH, Einhorn LH et al. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southestern Cancer Study Group. J Clin Oncol 1992; 10: 282–291.[Abstract]
3.
Tjan-Heijnen VCG, Postmus PE, Ardizzoni A et al. Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study. Ann Oncol 2001; 12: 1359–1368.
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